General Information of Drug Off-Target (DOT) (ID: OTG25JOG)

DOT Name Thyroid hormone receptor-associated protein 3 (THRAP3)
Synonyms BCLAF1 and THRAP3 family member 2; Thyroid hormone receptor-associated protein complex 150 kDa component; Trap150
Gene Name THRAP3
Related Disease
Hepatocellular carcinoma ( )
Advanced cancer ( )
Hyperglycemia ( )
Malignant tumor of parathyroid gland ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Parathyroid gland carcinoma ( )
UniProt ID
TR150_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15440
Sequence
MSKTNKSKSGSRSSRSRSASRSRSRSFSKSRSRSRSLSRSRKRRLSSRSRSRSYSPAHNR
ERNHPRVYQNRDFRGHNRGYRRPYYFRGRNRGFYPWGQYNRGGYGNYRSNWQNYRQAYSP
RRGRSRSRSPKRRSPSPRSRSHSRNSDKSSSDRSRRSSSSRSSSNHSRVESSKRKSAKEK
KSSSKDSRPSQAAGDNQGDEAKEQTFSGGTSQDTKASESSKPWPDATYGTGSASRASAVS
ELSPRERSPALKSPLQSVVVRRRSPRPSPVPKPSPPLSSTSQMGSTLPSGAGYQSGTHQG
QFDHGSGSLSPSKKSPVGKSPPSTGSTYGSSQKEESAASGGAAYTKRYLEEQKTENGKDK
EQKQTNTDKEKIKEKGSFSDTGLGDGKMKSDSFAPKTDSEKPFRGSQSPKRYKLRDDFEK
KMADFHKEEMDDQDKDKAKGRKESEFDDEPKFMSKVIGANKNQEEEKSGKWEGLVYAPPG
KEKQRKTEELEEESFPERSKKEDRGKRSEGGHRGFVPEKNFRVTAYKAVQEKSSSPPPRK
TSESRDKLGAKGDFPTGKSSFSITREAQVNVRMDSFDEDLARPSGLLAQERKLCRDLVHS
NKKEQEFRSIFQHIQSAQSQRSPSELFAQHIVTIVHHVKEHHFGSSGMTLHERFTKYLKR
GTEQEAAKNKKSPEIHRRIDISPSTFRKHGLAHDEMKSPREPGYKAEGKYKDDPVDLRLD
IERRKKHKERDLKRGKSRESVDSRDSSHSRERSAEKTEKTHKGSKKQKKHRRARDRSRSS
SSSSQSSHSYKAEEYTEETEEREESTTGFDKSRLGTKDFVGPSERGGGRARGTFQFRARG
RGWGRGNYSGNNNNNSNNDFQKRNREEEWDPEYTPKSKKYYLHDDREGEGSDKWVSRGRG
RGAFPRGRGRFMFRKSSTSPKWAHDKFSGEEGEIEDDESGTENREEKDNIQPTTE
Function
Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes.
Tissue Specificity Ubiquitous.
Reactome Pathway
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
PPARA activates gene expression (R-HSA-1989781 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Strong Biomarker [1]
Advanced cancer DISAT1Z9 Disputed Genetic Variation [2]
Hyperglycemia DIS0BZB5 Limited Altered Expression [3]
Malignant tumor of parathyroid gland DIS4X92K Limited Genetic Variation [4]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [3]
Obesity DIS47Y1K Limited Biomarker [3]
Parathyroid gland carcinoma DISEER2W Limited Genetic Variation [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [6]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [8]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [9]
Clozapine DMFC71L Approved Clozapine decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [10]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [16]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Thyroid hormone receptor-associated protein 3 (THRAP3). [17]
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⏷ Show the Full List of 10 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Thyroid hormone receptor-associated protein 3 (THRAP3). [12]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Thyroid hormone receptor-associated protein 3 (THRAP3). [13]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Thyroid hormone receptor-associated protein 3 (THRAP3). [15]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Thyroid hormone receptor-associated protein 3 (THRAP3). [15]
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References

1 Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.PLoS One. 2014 Dec 19;9(12):e114263. doi: 10.1371/journal.pone.0114263. eCollection 2014.
2 The RNA processing factors THRAP3 and BCLAF1 promote the DNA damage response through selective mRNA splicing and nuclear export.Nucleic Acids Res. 2017 Dec 15;45(22):12816-12833. doi: 10.1093/nar/gkx1046.
3 Thrap3 docks on phosphoserine 273 of PPAR and controls diabetic gene programming.Genes Dev. 2014 Nov 1;28(21):2361-9. doi: 10.1101/gad.249367.114. Epub 2014 Oct 14.
4 Complete genomic landscape of a recurring sporadic parathyroid carcinoma.J Pathol. 2013 Jul;230(3):249-60. doi: 10.1002/path.4203.
5 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
7 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
8 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
9 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
10 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
11 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
13 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
14 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
15 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
16 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
17 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.